ANATOMY AND PHARMACOLOGY OF FEAR-POTENTIATED STARTLE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 个体对特定压力源的弹性差异可能是由大脑中特定的神经肽受体模式介导的。在这里，我们探讨了这个问题，通过使用多变量的方法来确定大脑的网站，催产素（OTR），血管加压素（V1 aR），促肾上腺皮质激素释放因子1型（CRF 1）或2型受体结合共变与隔离引起的焦虑的措施：隔离增强惊吓（IPS）。使用相同的多元回归模型，在一组新动物中测量的相同三个结合位点/肽受体的线性组合成功预测了它们的IPS值。分组和隔离的动物之间的结合没有差异，这表明模式是性状效应，而不是隔离的结果。这些结果表明，综合活动的神经肽系统介导的社会行为和焦虑的基础IPS。 破伤风毒素轻链片段（LC）基因通过阻止突触囊泡释放来诱导突触抑制。第二个实验在大鼠中脑内应用这种方法，以证明LC基因表达可以在敏感的脑结构内实现功能和解剖学上的离散效应。虽然LC基因表达减少了线索特异性恐惧增强惊吓的绝对量，但它并没有减少线索增强惊吓的百分比，也没有减少恐惧诱导的背景冻结，非特异性运动活动或一般健康状况，表明其影响在功能和解剖学上是特异性的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Individual differences in resiliency to particular stressors may be mediated by specific neuropeptide receptor patterns in the brain. Here, we explored this issue by using a multivariate approach to identify brain sites in which oxytocin (OTR), vasopressin (V1aR), and corticotropin-releasing factor type 1 (CRF1) or type 2 receptor binding covaried with a measure of isolation-induced anxiety: isolation potentiated startle (IPS). Using the same multiple regression model, the linear combination of the same three binding sites/peptide receptors measured in a new group of animals successfully predicted their IPS values. There were no differences in binding between grouped and isolated animals, suggesting that the patterns are trait effects rather than a consequence of isolation. These results suggest that the integrated activity of neuropeptide systems mediating both social behavior and anxiety underlie IPS. The gene for the Light Chain fragment of Tetanus Toxin (LC) induces synaptic inhibition by preventing the release of synaptic vesicles. A second experiment applied this approach within the rat midbrain in order to demonstrate that LC gene expression can achieve functionally and anatomically discrete effects within a sensitive brain structure. Although LC gene expression reduced the absolute amount of cue-specific fear potentiated startle, it did not decrease percent potentiated startle to a cue, nor did it reduce fear-induced contextual freezing, nonspecific locomotor activity, or general health, indicating that its effects were functionally and anatomically specific.